Is ABCC2 p.Leu751Trp (c.2252T>G) pathogenic?

ABCC2 p.Leu751Trp (c.2252T>G) is classified Likely benign in ABCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-29). AlphaMissense: likely benign (0.1274); Absent from gnomAD v4.1.

How common is ABCC2 p.Leu751Trp (c.2252T>G) in the general population?

ABCC2 p.Leu751Trp (c.2252T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCC2 p.Leu751Trp (c.2252T>G)?

AlphaMissense predicts likely benign (score 0.1274) — an in-silico prediction, not a clinical call.

ABCC2 p.Leu751Trp

c.2252T>G · rs1590170184 · VCV680397

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1274 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1274	likely benign
REVEL	0.46	indeterminate
SaProt	LLR -11.90	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -2.4, phastCons 0.91
Regional constraint	o/e 0.98	unconstrained · MANE · 69 kb · p 0.48 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCC2
Protein: p.Leu751Trp
Coding: c.2252T>G
MANE Select: NM_000392
dbSNP: rs1590170184
Type: single nucleotide variant
Location: chr10:99817465 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB
Residue 751: an α-helix; the abc transporter 1 domain

Full ABCC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCC2 p.Leu751Phe Uncertain significance ★ ⚠ same residue
ABCC2 c.1031+4A>G Pathogenic/Likely pathogenic ★★ same type
ABCC2 c.1967+1G>A Pathogenic/Likely pathogenic ★★ same type
ABCC2 c.1968-1G>C Pathogenic/Likely pathogenic ★★ same type
ABCC2 c.3258+1G>A Pathogenic/Likely pathogenic ★★ same type
ABCC2 c.333+1G>A Likely pathogenic ★★ same type
ABCC2 c.3414+1G>A Likely pathogenic ★★ same type
ABCC2 c.3415-1G>A Pathogenic/Likely pathogenic ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/abcc2-p-leu751trp (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown